Synthesis of 3',3'-difluoro-2'- hydroxymethyl-4',5'-unsaturated carbocyclic nucleosides

3',3'-Difluoro-2'-hydroxymethyl-4',5'-unsaturated carbocyclic nucleosides 1-3 have been stereoselectively synthesized from ester 10, which can be conveniently prepared from 2,3-isopropylidene-d-glyceraldehyde 7 in five steps. The whole synthesis highlighted the stereoselective Reformatskii-Claisen rearrangement, ring-closing metathesis (RCM), and palladium-catalyzed allylic alkylation, in which the regioselectivity was reversed from that of nonfluorinated substrates.     

Synthesis of 3,4-dibromo-3,4,4-trichloro-1-phenylbutan-1-one and 1-aryl-2-bromo-3,4,4-trichlorobut-3-en-1-ones from 3,4,4-trichlorobut-3-enoic acid

Bromination of 3,4,4-trichlorobut-3-enoic acid in boiling carbon tetrachloride led to the formation of 2-bromo-3,4,4-trichlorobut-3-enoic acid as a result of replacement of hydrogen in the CH₂ group. The reaction at 40°C involved the double C=C bond to give 3,4-dibromo-3,4,4-trichlorobutanoic acid. The brominated acids were converted into the corresponding chlorides which were used to acylate benzene, toluene, and bromobenzene according to Friedel-Crafts. The acylation was not selective, and only the reaction of 3,4-dibromo-3,4,4-trichlorobutanoyl chloride with benzene gave 3,4-dibromo-3,4,4-trichloro-1-phenylbutan-1-one as the only product. 1-Aryl-2-bromo-3,4,4-trichlorobut-3-en-1-ones were synthesized by bromination of the corresponding 1-aryl-3,4,4-trichlorobut-3-en-1-ones which were prepared previously by Friedel-Crafts acylation of substituted benzenes with 3,4,4-trichlorobut-3-enoyl chloride.     

Synthesis and mesomorphic properties of 4-methoxyphenyl 4'- n -alkoxy-2',3',5',6'-tetrafluorobiphenyl-1-carboxylates

A novel type of 4-methoxyphenyl 4'- n -alkoxy-2',3',5',6'-tetrafluorobiphenyl-1-carboxylates have been synthesized. Textural observations by polarizing microscopy and DSC measurements of the phase transitions show that all of these compounds are thermotropic liquid crystals with only a nematic mesophase. The relationship between the properties and chemical structures of these compounds is discussed.     

Synthesis of Conformationally Locked Isonucleosides: 2'-Deoxy-2'-nucleobase-5'- deoxy-1', 4' : 3' , 6'-dianhydro-D-mannitol

IntroductionA novel class of nucleoside analogues, termed conformationa1ly locked nucleosides, hasattracted much attention owing to their conformationally restricted structures and their potentbiological activities. Griseolutic acids(I ), a family of naturally occurring bicyclic nucleosides,were isolated from StrePtomyces grisroaurantiacus and showed the inhibitory activities againstc--AMP phosphodiesterase and were able to induce the differentiation of murine neuroblas-tomaLl3. A large num…     

2',5'-二氢-1'H-吡咯骈[3',4':1,2][60]富勒烯衍生物的合成

以甘氨酸乙酯盐酸与取代的苯甲醛为原料,制得了一系列亚胺,然后用亚胺与C~6~0反应,得到带有不同取代基的吡咯烷骈[60]富勒烯衍生物.经^1HNMR,^1^3CNMR,FT-IR,UV-vis以及TOF-SMS等方法对所得化合物结构进行了表征,并进行了产物的生物活性测试。     

3-(2-二唑啉基)-色酮类化合物的合成研究

报道了取代的邻羟基苯乙酮(1a～1e)经Vilsmeier-Haack反应一步制得3-醛基色酮(2a～2e),2a～2e与取代的芳酰肼(3a～3c)缩合制得15个酰腙类化合物(4a～4o),4a～4o在醋酸酐作用下关环得15个3-(2-苝二唑啉基)-色酮(5a～5o),并通过元素分析,IR,~1H NMR和MS诺数据确证了上述化合物的结构。     

Synthesis of Conformationally Locked 2＇-Deoxy-2＇-nucleobase-5＇- Isonucleosides: 2＇-Deoxy-2＇-nucleobase-5＇ deoxy-1＇, 4＇ :3＇, 6＇-dianhydro-D-mannitol

Novel bicyclic isonucleosides, 2＇ -deoxy- 2＇ -nucleobase- 5＇ -deoxy- 1＇ , 4＇ : 3＇ , 6＇ -dianhydro D-mannitol 10a-10c, were synthesized from D-glucose. The computer-assisted molecular simu lation indicated that the sugar conformations of compounds 10a-10c were restricted to N-con formation.     

A Facile Total Synthesis of 2-Geranyl-2',3,4',4-tetrahydroxydihydrochalcone with Highly 5-Lipoxygenase Inhibiting Activity

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Chemical and structural implications of 1',2'- versus 2',4'- conformational constraints in the sugar moiety of modified thymine nucleosides

In order to understand how the chemical nature of the conformational constraint of the sugar moiety in ON/RNA(DNA) dictates the duplex structure and reactivity, we have determined molecular structures and dynamics of the conformationally constrained 1',2'-azetidine- and 1',2'-oxetane-fused thymidines, as well as their 2',4'-fused thymine (T) counterparts such as LNA-T, 2'-amino LNA-T, ENA-T, and aza-ENA-T by NMR, ab initio (HF/6-31G** and B3LYP/6-31++G**), and molecular dynamics simulations (2 ns in the explicit aqueous medium). It has been found that, depending upon whether the modification leads to a bicyclic 1',2'-fused or a tricyclic 2',4'-fused system, they fall into two distinct categories characterized by their respective internal dynamics of the glycosidic and the backbone torsions as well as by characteristic North-East type sugar conformation (P = 37 degrees +/- 27 degrees , phi(m) = 25 degrees +/- 18 degrees ) of the 1',2'-fused systems, and (ii) pure North type (P = 19 degrees +/- 8 degrees , phi(m) = 48 degrees +/- 4 degrees ) for the 2',4'-fused nucleosides. Each group has different conformational hyperspace accessible, despite the overall similarity of the North-type conformational constraints imposed by the 1',2'- or 2',4'-linked modification. The comparison of pK(a)s of the 1-thyminyl aglycon as well as that of endocyclic sugar-nitrogen obtained by theoretical and experimental measurements showed that the nature of the sugar conformational constraints steer the physicochemical property (pK(a)) of the constituent 1-thyminyl moiety, which in turn can play a part in tuning the strength of hydrogen bonding in the basepairing.     

Synthesis of novel L-2',3'-dideoxy-2'-trifluoromethyl-4'- thiocytidines from alpha-trifluoromethyl-alpha,beta-unsaturated ester

A short and efficient synthesis of L-2',3'-dideoxy-2'-trifluoromethyl-4'-thiocytidines is described. (2R,4S/2S,4S)-5-(tert-Butyldimethylsiloxy)-2-trifluoromethylpentan-4-olide (3a and 3b) are prepared from alpha-trifluoromethyl-alpha,beta-unsaturated ester (1) in three steps and converted to compounds 6a and 6b. The corresponding 1-O-acetyl derivatives 8a and 8b were obtained via the usual Pummerer rearrangement from 6a and 6b in two steps, which were in turn used to synthesize L-4'-thiocytidines 10a and 10b.     

Trinuclear copper(II) complex showing high selectivity for the hydrolysis of 2'-5' over 3'-5' for UpU and 3'-5' over 2'-5' for ApA ribonucleotides

The cooperative action of multiple Cu(II) nuclear centers is shown to be effective and selective in the hydrolysis of 2'-5' and 3'-5' ribonucleotides. Reported herein is the specific catalysis by two trinuclear Cu(II) complexes of L3A and L3B. Pseudo first-order kinetic studies reveal that the L3A trinuclear Cu(II) complex effects hydrolysis of Up(2'-5')U with a rate constant of 28 x 10(-)(4) min(-)(1) and Up(3'-5')U with a rate constant of 0.5 x 10(-)(4) min(-)(1). The hydrolyses of Ap(3'-5')A and Ap(2'-5')A proceed with rate constants of 24 x 10(-)(4) min(-)(1) and 0.5 x 10(-)(4) min(-)(1) respectively. The L3A trinuclear Cu(II) complex demonstrates high specificity for Up(2'-5')U and Ap(3'-5')A. Similar studies with the more rigid L3B trinuclear Cu(II) complex shows no selectivity and yields lower rate constants for hydrolysis. The selectivity observed with the L3A ligand is attributed to the geometry of the ligand-bound diribonucleotide which ultimately dictates the proximity of the attacking hydroxyl and the phosphoester to a Cu(II) center for activation and subsequent hydrolysis.     

Synthesis of Stereoisomers of Cryptofolione 6'-Mono- and 4', 6'-Di-O-benzyl Ethers

Synthesis of stereoisomers of 6′‐mono‐ and 4′,6′‐di‐O‐benzyl cryptofolione is described through a key intermediate 6 , which was prepared by coupling of iodobenzene 8 with chiral propargyl alcohol 9 under Cosford protocol conditions. Monobenzyl ether 4 is obtained via epoxide 6 opening with vinyl Grignard, followed by cross‐metathesis reaction with a vinyl lactone 11 . Whereas, dibenzyl ether 5 is prepared by epoxide 6 opening with chiral propargyl alcohol 7 followed by simple transformations and finally cis‐Wittig olefination.     

3,4′,5-三甲氧基-1,2-二苯乙烯合成、晶体结构与量子化学研究

利用Wittig-Horner反应制备了抗癌保健药物白藜芦醇的前体化合物3,4′,5-三甲氧基-1,2-二苯乙烯,单晶结构解析结果表明,该晶体属于三斜晶系,空间群P1,晶胞参数:a=0.9960(12)nm,b=1.0040(12)nm,c=1.6194(19)nm,α=90.702(2)°,β=105.515(2)°,γ=111.815(2)°,V=1.6194(3)nm3,Dc=1.249Mg/m3,结构基元分子数Z=2.对晶体结构的结构基元进行了量子化学研究,计算结果表明,3,4′,5-三甲氧基-1,2-二苯乙烯晶体结构基元与组成结构基元分子两种不同构象能量和的差值为ΔEBSSE=5.51kJ/mol.因此,晶体结构基元中两种构象之间存在π-π堆积相互作用.     

Synthesis and Study of Lactim Ethers of 3,4-Dihydrocarbostyryl and 2,3,4,5-Tetrahydrobenz[b]azepin-2-one

Alkylation of 3,4-dihydrocarbostyryl and 2,3,4,5-tetrahydrobenz[b]azepin-2-one using dimethyl sulfate and triethyloxonium fluoborate gives the corresponding lactim ethers. The reactions of lactim ethers with different compounds having primary amino groups (including ammonia, alkyl-, aralkyl-, and arylamines, amino acids, and related compounds) have been studied. Novel heterocyclic compounds based on the lactim ethers have been synthesized.